(+)-3-( sup 123 I)Iodo-MK-801: Synthesis and characterization of binding to the N-methyl-D-aspartate receptor complex
- Merck Sharp Dohme Research Labs., West Point, PA (USA)
Synthetic methods have been established for preparing high specific activity (+)-3-({sup 123}I)Iodo-MK-801 in high radiochemical yield. The binding of the radiotracer to rat cortical membranes has been examine to assess its potential use as an in vivo imaging agent for the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. Under the conditions of the assay, specific (+)-3-({sup 123}I)Iodo-MK-801 binding to membrane homogenates represented greater than 95% of the total binding. Several structurally distinct, noncompetitive NMDA receptor antagonists inhibited binding with potencies in accordance with their reported inhibitory activity at the receptor complex. The concentration of ({plus minus})-3-Iodo-MK-801 required to inhibit 50% of (+)-3-({sup 123}I)Iodo-MK-801 binding (IC{sub 50}) was 3.4 nM when using a low ionic strength assay buffer and 5.5 nM in a physiological buffer. In a thoroughly washed membrane preparation, (+)-3-({sup 123}I)Iodo-MK-801 binding was enhanced by L-glutamate and glycine at concentrations known to activate the NMDA receptor. The results indicate that (+)-3-({sup 123}I)Iodo-MK-801 specifically labels the NMDA receptor complex in rat brain membranes and the retention of high affinity under near physiological assay conditions suggests that it may be useful as a SPECT imaging agent for the receptor in vivo.
- OSTI ID:
- 6969478
- Journal Information:
- Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 46:15; ISSN 0024-3205; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
ASPARTIC ACID
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL COMPOSITION
CHEMICAL PREPARATION
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 123
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
SYNTHESIS
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES